Trial Outcomes & Findings for Study to Asses Pharmacodynamics, Pharmacokinetics, Safety and Tolerability of AZD0328 in Patients With Schizophrenia (NCT NCT00669903)
NCT ID: NCT00669903
Last Updated: 2010-08-06
Results Overview
The GMLT and OCLT standardized change composite score will be calculated as the mean of the GMLT and OCLT standardized change from baseline scores. Least square means were derived using a mixed effects repeated measures model with protocol scheduled assessment day, treatment group, baseline score, and assessment day-by-treatment interaction as fixed factors, center as a random factor, and baseline score as a covariate. Scale range from negative infinity (worst value) to positive infinity (best value).
TERMINATED
PHASE2
100 participants
Baseline and Day 14
2010-08-06
Participant Flow
A total of two US centers were inititated with first patient enrolled on 2 April 2008 and last patient completed on 4 November 2008. A total of 158 patients were enrolled with 100 patients allocated to randomized treatment.
Patients were to receive a stable dose of an antipsychotic for the 4 weeks prior to randomization, have stable psychotic symptoms without a hospitalization for the 8 weeks prior to randomization, and were to be smoking an average of \>=10 cigarettes per day. Enrolled patients who no longer met entry criteria at randomization were not randomized.
Participant milestones
| Measure |
AZD0328 Low Dose Group
AZD0328 Low dose group (0.00093 to 0.0028 mg oral solution)
|
AZD0328 Optimal Dose Group
AZD0328 Optimal dose group (0.0048 to 0.0329 mg oral solution)
|
AZD0328 High Dose Group
AZD0328 High dose group (0.075 to 0.675 mg oral solution)
|
Placebo
Placebo
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
23
|
37
|
18
|
22
|
|
Overall Study
Completed Treatment Period
|
23
|
33
|
13
|
19
|
|
Overall Study
COMPLETED
|
22
|
32
|
13
|
18
|
|
Overall Study
NOT COMPLETED
|
1
|
5
|
5
|
4
|
Reasons for withdrawal
| Measure |
AZD0328 Low Dose Group
AZD0328 Low dose group (0.00093 to 0.0028 mg oral solution)
|
AZD0328 Optimal Dose Group
AZD0328 Optimal dose group (0.0048 to 0.0329 mg oral solution)
|
AZD0328 High Dose Group
AZD0328 High dose group (0.075 to 0.675 mg oral solution)
|
Placebo
Placebo
|
|---|---|---|---|---|
|
Overall Study
Adverse Event
|
0
|
1
|
3
|
1
|
|
Overall Study
Withdrawal by Subject
|
0
|
2
|
2
|
2
|
|
Overall Study
Lost to Follow-up
|
1
|
1
|
0
|
1
|
|
Overall Study
Protocol Violation
|
0
|
1
|
0
|
0
|
Baseline Characteristics
Study to Asses Pharmacodynamics, Pharmacokinetics, Safety and Tolerability of AZD0328 in Patients With Schizophrenia
Baseline characteristics by cohort
| Measure |
AZD0328 Low Dose Group
n=23 Participants
AZD0328 Low dose group (0.00093 to 0.0028 mg oral solution)
|
AZD0328 Optimal Dose Group
n=37 Participants
AZD0328 Optimal dose group (0.0048 to 0.0329 mg oral solution)
|
AZD0328 High Dose Group
n=18 Participants
AZD0328 High dose group (0.075 to 0.675 mg oral solution)
|
Placebo
n=22 Participants
Placebo
|
Total
n=100 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Race/Ethnicity, Customized
Caucasian
|
4 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
10 Participants
n=21 Participants
|
|
Age Continuous
|
38.5 Years
STANDARD_DEVIATION 11.2 • n=5 Participants
|
41.7 Years
STANDARD_DEVIATION 9.2 • n=7 Participants
|
38.3 Years
STANDARD_DEVIATION 9.8 • n=5 Participants
|
40.0 Years
STANDARD_DEVIATION 9.8 • n=4 Participants
|
40.0 Years
STANDARD_DEVIATION 9.9 • n=21 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
10 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
22 Participants
n=5 Participants
|
33 Participants
n=7 Participants
|
15 Participants
n=5 Participants
|
20 Participants
n=4 Participants
|
90 Participants
n=21 Participants
|
|
Race/Ethnicity, Customized
Black
|
18 Participants
n=5 Participants
|
33 Participants
n=7 Participants
|
17 Participants
n=5 Participants
|
18 Participants
n=4 Participants
|
86 Participants
n=21 Participants
|
|
Race/Ethnicity, Customized
Other
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
4 Participants
n=21 Participants
|
|
Baseline Positive and Negative Syndrome Scale (PANSS) total score
|
67.9 Points of PANSS score
STANDARD_DEVIATION 10.3 • n=5 Participants
|
71.8 Points of PANSS score
STANDARD_DEVIATION 12.0 • n=7 Participants
|
72.1 Points of PANSS score
STANDARD_DEVIATION 12.2 • n=5 Participants
|
69.5 Points of PANSS score
STANDARD_DEVIATION 13.2 • n=4 Participants
|
70.4 Points of PANSS score
STANDARD_DEVIATION 11.9 • n=21 Participants
|
PRIMARY outcome
Timeframe: Baseline and Day 14The GMLT and OCLT standardized change composite score will be calculated as the mean of the GMLT and OCLT standardized change from baseline scores. Least square means were derived using a mixed effects repeated measures model with protocol scheduled assessment day, treatment group, baseline score, and assessment day-by-treatment interaction as fixed factors, center as a random factor, and baseline score as a covariate. Scale range from negative infinity (worst value) to positive infinity (best value).
Outcome measures
| Measure |
AZD0328 Low Dose Group
n=23 Participants
AZD0328 Low dose group (0.00093 to 0.0028 mg oral solution)
|
AZD0328 Optimal Dose Group
n=32 Participants
AZD0328 Optimal dose group (0.0048 to 0.0329 mg oral solution)
|
AZD0328 High Dose Group
n=13 Participants
AZD0328 High dose group (0.075 to 0.675 mg oral solution)
|
Placebo
n=19 Participants
Placebo
|
|---|---|---|---|---|
|
CogState Groton Maze Learning Task (GMLT) and One Card Learning Task (OCLT) Standardized Composite Score at Day 14
|
0.234 units on a scale
Standard Error 0.122 • Interval 0.122 to
|
0.240 units on a scale
Standard Error 0.072 • Interval 0.072 to
|
0.194 units on a scale
Standard Error 0.216 • Interval 0.216 to
|
0.266 units on a scale
Standard Error 0.099 • Interval 0.099 to
|
SECONDARY outcome
Timeframe: Baseline and Day 14GMLT score is defined as the -log10 transform of the sum of the number of errors made during GMLT trials. Mean GMLT score was calculated as the average of the 2 hour, 5 hour, and 8 hour scores. The GMLT standardized change score was calculated as the change from baseline in the mean GMLT score divided by the within subject standard deviation. Scale range from negative infinity (worst value) to positive infinity (best value).
Outcome measures
| Measure |
AZD0328 Low Dose Group
n=23 Participants
AZD0328 Low dose group (0.00093 to 0.0028 mg oral solution)
|
AZD0328 Optimal Dose Group
n=32 Participants
AZD0328 Optimal dose group (0.0048 to 0.0329 mg oral solution)
|
AZD0328 High Dose Group
n=13 Participants
AZD0328 High dose group (0.075 to 0.675 mg oral solution)
|
Placebo
n=19 Participants
Placebo
|
|---|---|---|---|---|
|
CogState Groton Maze Learning Task (GMLT) Standardized Change Score at Day 14
|
0.313 units on a scale
Standard Error 0.163 • Interval 0.163 to
|
0.360 units on a scale
Standard Error 0.104 • Interval 0.104 to
|
0.281 units on a scale
Standard Error 0.249 • Interval 0.249 to
|
0.235 units on a scale
Standard Error 0.124 • Interval 0.124 to
|
SECONDARY outcome
Timeframe: Baseline and Day 14OCLT score is defined as the arcsine transform of the proportion of correct responses during OCLT trials. Mean OCLT score was calculated as the average of the 2 hour, 5 hour, and 8 hour scores. The OCLT standardized change score was calculated as the change from baseline in the mean OCLT score divided by the within-subject standard deviation. Scale range from negative infinity (worst value) to positive infinity (best value).
Outcome measures
| Measure |
AZD0328 Low Dose Group
n=23 Participants
AZD0328 Low dose group (0.00093 to 0.0028 mg oral solution)
|
AZD0328 Optimal Dose Group
n=33 Participants
AZD0328 Optimal dose group (0.0048 to 0.0329 mg oral solution)
|
AZD0328 High Dose Group
n=13 Participants
AZD0328 High dose group (0.075 to 0.675 mg oral solution)
|
Placebo
n=19 Participants
Placebo
|
|---|---|---|---|---|
|
CogState One Card Learning Task (OCLT) Standardized Change Score at Day 14
|
0.150 units on a scale
Standard Error 0.126 • Interval 0.126 to
|
0.102 units on a scale
Standard Error 0.100 • Interval 0.1 to
|
0.094 units on a scale
Standard Error 0.232 • Interval 0.232 to
|
0.316 units on a scale
Standard Error 0.152 • Interval 0.152 to
|
SECONDARY outcome
Timeframe: Baseline and Day 14DT score is defined as -1 times the mean of log10 transformed reaction times for all correct responses. Mean DT score was calculated as the average of the 2 hour, 5 hour, and 8 hour scores. The DT standardized change score will be calculated as the change from baseline in the mean DT score divided by the within-subject standard deviation. Score range from negative infinity (worst value) to positive infinity (best value).
Outcome measures
| Measure |
AZD0328 Low Dose Group
n=23 Participants
AZD0328 Low dose group (0.00093 to 0.0028 mg oral solution)
|
AZD0328 Optimal Dose Group
n=33 Participants
AZD0328 Optimal dose group (0.0048 to 0.0329 mg oral solution)
|
AZD0328 High Dose Group
n=13 Participants
AZD0328 High dose group (0.075 to 0.675 mg oral solution)
|
Placebo
n=19 Participants
Placebo
|
|---|---|---|---|---|
|
CogState Detection Task (DT) Standardized Change Score at Day 14
|
0.116 units on a scale
Standard Error 0.116 • Interval 0.116 to
|
-0.014 units on a scale
Standard Error 0.115 • Interval 0.115 to
|
-0.095 units on a scale
Standard Error 0.158 • Interval 0.158 to
|
0.098 units on a scale
Standard Error 0.095 • Interval 0.095 to
|
SECONDARY outcome
Timeframe: Baseline and Day 14IT score defined as 1 times the mean of log10 transformed reaction times for all correct responses. Mean IT score calculated as the average of the 2 hour, 5 hour, and 8 hour scores. The IT standardized change score will be calculated as the change from baseline in the mean IT score divided by the within-subject standard dev. Least square means were derived using a mixed effects repeated measures model with protocol scheduled assessment day, treatment group, baseline score, and assessment day-by-treatment interaction as fixed factors, center as a random factor, and baseline score as a covariate
Outcome measures
| Measure |
AZD0328 Low Dose Group
n=23 Participants
AZD0328 Low dose group (0.00093 to 0.0028 mg oral solution)
|
AZD0328 Optimal Dose Group
n=33 Participants
AZD0328 Optimal dose group (0.0048 to 0.0329 mg oral solution)
|
AZD0328 High Dose Group
n=13 Participants
AZD0328 High dose group (0.075 to 0.675 mg oral solution)
|
Placebo
n=19 Participants
Placebo
|
|---|---|---|---|---|
|
CogState Identification Task (IT) Standardized Change Score at Day 14
|
-0.145 unit on a scale
Standard Error 0.177 • Interval 0.177 to
|
-0.049 unit on a scale
Standard Error 0.121 • Interval 0.121 to
|
-0.173 unit on a scale
Standard Error 0.136 • Interval 0.136 to
|
-0.103 unit on a scale
Standard Error 0.132 • Interval 0.132 to
|
SECONDARY outcome
Timeframe: Baseline and Day 14GMRT score defined as the -log10 transform of the sum of the number of errors made during GMRT trials. Mean GMRT score calculated as the average of the 2 hour, 5 hour, and 8 hour scores. The GMRT standardized change score was calculated as change from baseline in mean GMRT score divided by the within subject standard deviation. Least square means were derived using a mixed effects repeated measures model with protocol scheduled assessment day, treatment group, baseline score, assessment day-by-treatment interaction as fixed factors, center as random factor, and baseline score as a covariate
Outcome measures
| Measure |
AZD0328 Low Dose Group
n=23 Participants
AZD0328 Low dose group (0.00093 to 0.0028 mg oral solution)
|
AZD0328 Optimal Dose Group
n=33 Participants
AZD0328 Optimal dose group (0.0048 to 0.0329 mg oral solution)
|
AZD0328 High Dose Group
n=13 Participants
AZD0328 High dose group (0.075 to 0.675 mg oral solution)
|
Placebo
n=19 Participants
Placebo
|
|---|---|---|---|---|
|
CogState Groton Maze Recall Task (GMRT) Standardized Change Score at Day 14
|
0.213 unit on a scale
Standard Error 0.139 • Interval 0.139 to
|
0.406 unit on a scale
Standard Error 0.112 • Interval 0.112 to
|
0.467 unit on a scale
Standard Error 0.263 • Interval 0.263 to
|
0.409 unit on a scale
Standard Error 0.183 • Interval 0.183 to
|
Adverse Events
AZD0328 Low Dose Group
AZD0328 Optimal Dose Group
AZD0328 High Dose Group
Placebo
Serious adverse events
| Measure |
AZD0328 Low Dose Group
n=23 participants at risk
AZD0328 Low dose group (0.00093 to 0.0028 mg oral solution)
|
AZD0328 Optimal Dose Group
n=37 participants at risk
AZD0328 Optimal dose group (0.0048 to 0.0329 mg oral solution)
|
AZD0328 High Dose Group
n=18 participants at risk
AZD0328 High dose group (0.075 to 0.675 mg oral solution)
|
Placebo
n=22 participants at risk
Placebo
|
|---|---|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary Embolism
|
0.00%
0/23
|
0.00%
0/37
|
0.00%
0/18
|
4.5%
1/22
|
Other adverse events
| Measure |
AZD0328 Low Dose Group
n=23 participants at risk
AZD0328 Low dose group (0.00093 to 0.0028 mg oral solution)
|
AZD0328 Optimal Dose Group
n=37 participants at risk
AZD0328 Optimal dose group (0.0048 to 0.0329 mg oral solution)
|
AZD0328 High Dose Group
n=18 participants at risk
AZD0328 High dose group (0.075 to 0.675 mg oral solution)
|
Placebo
n=22 participants at risk
Placebo
|
|---|---|---|---|---|
|
Gastrointestinal disorders
DYSPEPSIA
|
39.1%
9/23
|
27.0%
10/37
|
27.8%
5/18
|
18.2%
4/22
|
|
Nervous system disorders
HEADACHE
|
26.1%
6/23
|
10.8%
4/37
|
33.3%
6/18
|
18.2%
4/22
|
|
Musculoskeletal and connective tissue disorders
MYALGIA
|
4.3%
1/23
|
13.5%
5/37
|
5.6%
1/18
|
4.5%
1/22
|
|
Gastrointestinal disorders
NAUSEA
|
4.3%
1/23
|
5.4%
2/37
|
22.2%
4/18
|
0.00%
0/22
|
|
Gastrointestinal disorders
CONSTIPATION
|
13.0%
3/23
|
8.1%
3/37
|
0.00%
0/18
|
4.5%
1/22
|
|
Psychiatric disorders
INSOMNIA
|
0.00%
0/23
|
8.1%
3/37
|
11.1%
2/18
|
0.00%
0/22
|
|
Nervous system disorders
LETHARGY
|
0.00%
0/23
|
10.8%
4/37
|
5.6%
1/18
|
0.00%
0/22
|
|
Nervous system disorders
SEDATION
|
4.3%
1/23
|
5.4%
2/37
|
11.1%
2/18
|
4.5%
1/22
|
|
Psychiatric disorders
ANXIETY
|
0.00%
0/23
|
5.4%
2/37
|
11.1%
2/18
|
4.5%
1/22
|
|
Respiratory, thoracic and mediastinal disorders
COUGH
|
4.3%
1/23
|
8.1%
3/37
|
0.00%
0/18
|
0.00%
0/22
|
|
Respiratory, thoracic and mediastinal disorders
NASAL CONGESTION
|
8.7%
2/23
|
2.7%
1/37
|
5.6%
1/18
|
0.00%
0/22
|
|
Gastrointestinal disorders
TOOTHACHE
|
13.0%
3/23
|
2.7%
1/37
|
0.00%
0/18
|
0.00%
0/22
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee No publication or presentation of results until the earlier of the publication of the first multi-center publication and the second anniversary of the completion of the multi-center study at all sites. Sponsor must receive a copy of proposed manuscript for review and comment at least 60 days prior to its submission for publication or presentation.
- Publication restrictions are in place
Restriction type: OTHER